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Doravirine, Rifapentine and Isoniazid Interaction (DORIIS)

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ClinicalTrials.gov Identifier: NCT03886701
Recruitment Status : Completed
First Posted : March 22, 2019
Results First Posted : March 3, 2020
Last Update Posted : March 27, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Walter K. Kraft, Thomas Jefferson University

Tracking Information
First Submitted Date  ICMJE March 12, 2019
First Posted Date  ICMJE March 22, 2019
Results First Submitted Date  ICMJE February 13, 2020
Results First Posted Date  ICMJE March 3, 2020
Last Update Posted Date March 27, 2020
Actual Study Start Date  ICMJE April 22, 2019
Actual Primary Completion Date May 20, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 16, 2020)
  • Doravirine Maximum Concentration (Cmax) [ Time Frame: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose ]
    Doravirine maximum observed concentration during the dosing interval
  • Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12) [ Time Frame: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose ]
    Doravirine area under the plasma-concentration time curve derived from plasma sampling during one dosing interval
  • Doravirine Oral Clearance (CL/F) [ Time Frame: Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose ]
    Doravirine apparent oral clearance derived from plasma sampling
Original Primary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
  • Cmax [ Time Frame: Days 4 and 21 ]
    Peak plasma concentration
  • Tmax [ Time Frame: Days 4 and 21 ]
    Time to maximum plasma concentration
  • AUC0-T [ Time Frame: Days 4-7 and 21-24 ]
    Area under the plasma-concentration time curve
  • CL/F [ Time Frame: Days 4-7 and 21-24 ]
    Apparent oral clearance
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2020)
Adverse Event [ Time Frame: Days 1-24 post-dose (period 1 and 2) and 31-34 post-dose (post-study) ]
Safety and tolerability
Original Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
Adverse Event [ Time Frame: Days 1-24 and 31-34 ]
Safety
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Doravirine, Rifapentine and Isoniazid Interaction
Official Title  ICMJE A Phase 1, Open-Label, Fixed-Sequence, Drug Interaction Study to Investigate the Effect of Once-Weekly Rifapentine and Isoniazid on the Pharmacokinetics of Steady-State Doravirine
Brief Summary Drug therapy for persons living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) co-infected with latent tuberculosis infection (LTBI) is complex. Anti-tuberculosis drugs used to treat LTBI often induce drug metabolizing enzymes that share the same metabolic pathway as antiretroviral drugs used for those living with HIV/AIDS. This study evaluates the drug-drug interaction (DDI) potential of an antiretroviral drug when co-administered with a common anti-tuberculosis regimen of drugs.
Detailed Description

Rifapentine (RPT) and isoniazid (INH) given once weekly for 12 weeks is commonly used for treating LTBI in adults. For people living with HIV-1, the risks of LTBI is increased. Individuals living with HIV-1 are often on chronic antiretroviral drugs that prevent immunodeficiency and complications associated with infection. Unfortunately, antiretroviral drugs are subject to many DDIs especially with RPT which induces drug clearing enzymes.

Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection. Because RPT induces the metabolic pathway in which DOR is removed, there is concern that taking both concomitantly will result in an unwanted DDI leading to reduced DOR concentrations in the blood. Reduced levels will result in loss of efficacy for the drug and therefore not provide adequate viral suppression in those living with HIV. This study investigates the DDI potential of the once weekly regimen RPT and INH together with DOR in healthy volunteers.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Latent Tuberculosis
  • Human Immunodeficiency Virus
  • Rifamycins Causing Adverse Effects in Therapeutic Use
  • Drug Interaction Potentiation
Intervention  ICMJE
  • Drug: Doravirine (DOR)
    Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.
    Other Name: Pifeltro
  • Drug: Rifapentine (RPT)
    Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
    Other Name: Priftin
  • Drug: Isoniazid (INH)
    Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.
    Other Name: Generic (various)
Study Arms  ICMJE Experimental: Experimental
Period 1: DOR twice-daily alone (Study days 1-4) and Period 2: DOR twice-daily with RPT and INH once-weekly (Study days 7-21)
Interventions:
  • Drug: Doravirine (DOR)
  • Drug: Rifapentine (RPT)
  • Drug: Isoniazid (INH)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 21, 2019)
11
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 20, 2019
Actual Primary Completion Date May 20, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Healthy male or female between 18-60 years old at the time of screening.
  2. Have a Body Mass Index (BMI) > 19 and < 33.
  3. Weigh > 45 kg but < 120 kg.
  4. Non-smoker (tobacco or electronic cigarettes).
  5. Negative QuantiFERON-TB Gold at screening.
  6. Subjects who agree to abstain from alcohol consumption throughout the duration of the study.
  7. Female subjects of childbearing potential must demonstrate a urine beta-hCG consistent with non-pregnancy at the time of the screening visit and agree to the use (and/or have their partner use) of an acceptable method of birth-control at initial screening, during the time of the trial and until two weeks after the last dose of drug following the last treatment period.
  8. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

Exclusion Criteria:

  1. History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, dermatologic, psychiatric abnormalities or neurological (including stroke and chronic seizure) diseases.
  2. >500 mL blood or plasma donation in the 6 weeks prior to study start
  3. Known anaphylactic or severe systemic reactions to any components of doravirine, rifapentine, isoniazid or pyridoxine.
  4. Positive HIV, Hepatitis B or Hepatitis C virus. Evidence of prior Hepatitis B infection and immunity is not exclusionary.
  5. Latent or active tuberculosis infection. Documented prior fully treated latent tuberculosis is not exclusionary.
  6. Females who are postpartum < 12 months.
  7. Current drug or alcohol abuse.
  8. Received study drug in another study within 4 weeks or within 5 half-lives, which ever occurring first, before first anticipated dose of study drug in this study.
  9. Unable to refrain from use of over-the-counter, prescription (unless determined appropriate by the investigator), herbal or natural products, vitamins or supplements, or grapefruit juice/grapefruit products.
  10. Any clinical significant findings on lab, ECG or physical exam at screening.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03886701
Other Study ID Numbers  ICMJE 12690
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Walter K. Kraft, Thomas Jefferson University
Study Sponsor  ICMJE Walter K. Kraft
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Walter K Kraft, MD Sidney Kimmel Medical College at Thomas Jefferson University
PRS Account Thomas Jefferson University
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP